The present project is designed to test the hypothesis that post-axotomy induced sprouting of Abeta primary afferent fibers into lamina II underlies neuropathic pain. The tests of this hypothesis are 1) to correlate the behavioral changes (mechanical allodynia, cold allodynia, ongoing pain) with the morphologic changes (loss of DRG cells, DRG axons and central synapses, sprouting of Abeta fibers in lamina II), and 2) to prevent the morphologic changes and show that the pain behavior does not develop. The system used for these tests in transection of the L5 and L6 spinal nerves in the rat (the Chung model), which results in consistent neuropathic pain. The reasoning is that peripheral sensory axotomy results in death of some DRG cells, with subsequent central denervation, and priming of the others. This combination of central denervation and primed cells results in sprouting of central fibers into the denervated areas. In particular we have found that Abeta fibers sprout into lamina II after nerve lesions. We hypothesize that the entrance of large sensory fibers normally concerned with light touch and fine discrimination into a region that normally processes nociceptive input plays a role in the production of certain types of pain. A key part of this project is to stop the Abeta sprouting into lamina II. Our proposed way to do this is to stop the loss of DRG cells. Our reasoning is that this will stop loss of central primary afferent synapses, and if so, there would be no synaptic vacancies in the cord and thus no place for activated fibers to sprout. Two procedures in our opinion give best chance for stopping loss of sensory cells after nerve lesions, administration of nerve growth factor (NGF) to the central stumps or placement of the transected nerve stumps in an impermeable tube.